Modified Vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus that cannot replicate in human cells. It is expected to have a better safety profile than the traditional smallpox vaccines. The clinical trials is a phase I/II, randomized, placebo-controlled, double-blinded, schedule-finding study of MVA. The hypothesis is that MVA will be safe in humans when administered by intramuscular (IM) injection and will result in an immune response comparable to that observed after Dryvax immunization. Subjects are randomized to one or two injections with MVA or placebo, followed by Dryvax challenge 12 weeks later. Safety evaluations are performed on an ongoing basis throughout the study and immunogenicity samples are collected and frozen for batch testing by research laboratories. Interim safety data were reviewed by the Intramural Data and Safety Monitoring Board on 6/9/03.